The function of Fc receptors in mouse spleen lymphocytes was studied by examining the effect of immobilized antigen-antibody complexes on DNA synthesis induced by various mitogens and on antibody synthesis induced by antigen and B cell mitogens. It was found that the mitogenic stimulation of cells bearing Fc receptors was dramatically inhibited by immobilized antigen-antibody complexes. This inhibition was Fc specific and did not occur when the cells were presented with soluble antigen-antibody complexes. This effect was seen with LPS, lipid A, PPD, poly I:C, cGMP and Con A. However, the mitogenic effect of PHA, which stimulates a subset of T cells not possessing the Fc receptor, was not depressed by immobilized complexes. The LPS mitogenic effect was inhibited in both normal and congenitally athymic mice. A similar inhibition of the polyclonal production of antibody forming cells by LPS was observed when the cultures were carried out in the absence of xenogeneic serum. These results suggest that the Fc receptor may function to generate an intracellular "off" signal for proliferation and differentiation and may play a role in the regulation of the immune response.